As of Jan. 1, 1991, over 16,000 heart transplants have taken place worldwide, more than 87% of these since 1984 (according to Kreitt et al., "The Registry of the International Society for Heart and Lung Transplantation: Eight Annual Report", The Journal of Heart and Lung Transplantation, Number 4, Jul.-Aug. 1991, pp. 491-498). Rejection of the transplanted heart within two years is the cause of death in 40% or more of all cases. Currently, the preferred method for monitoring rejection is by serial transvenous endomyocardial biopsy. Such a procedure is invasive and relatively traumatic, and must usually be performed at specialized facilities. Typically, two such tests are performed during the first six post-implant months; thereafter, the tests are given less frequently, but throughout the patient's lifetime. Up to a day may be required to obtain results from such a test. One known shortcoming of the serial transvenous endomyocardial biopsy in evaluating heart rejection is that existing scar tissue in the heart, which can occur for various reasons other than heart rejection, can be erroneously interpreted as indicating rejection.
It has also been found, however, that certain features of the electrical cardiac signal in transplant patients may also be utilized as an indicator of heart rejection. See, e.g., Warnecke et al., "Noninvasive Monitoring of Cardiac Allograft Rejection by Intramyocardial Electrogram Recordings", Circulation 74 (suppl. III), III-72-III-76, 1986. In particular, it has been found that the onset of heart rejection is accompanied by a reduction of up to 15% in the magnitude of intracardiac R-wave and T-wave peaks. See, e.g., Rosenbloom et al., "Noninvasive Detection of Cardiac Allograft Rejection by Analysis of the Unipolar Peak-to-Peak Amplitude of Intramyocardial Electrograms", Ann. Thorac. Surg., 1989; 47:407-411; see also, e.g., Grace et al., "Diagnosis of Early Cardiac Transplant Rejection by Fall in Evoked T Wave Amplitude Measured Using an Externalized QT Driven Rate Responsive Pacemaker", PACE, vol. 14, Jun. 1991. The ability to monitor and detect this phenomenon would therefore facilitate the early detection and treatment of rejection. To this end, an implantable pacemaker with an accurate analog telemetry channel for transmitting intracardiac signals would greatly enhance the ability of a monitoring physician to assess the cardiac condition.
Intracardiac electrogram signals have been used to evaluate heart rejection. Typically, however, several or perhaps up to five or more epicardial leads may be used for this purpose, since it is believed that the manifestations of heart rejection are initially localized and can begin at various sites in the heart muscle.
The intracardiac leads associated with an implanted pacemaker might also be used in the evaluation of cardiac signals. Unfortunately, even today's state-of-the-art pacemakers have rather inaccurate telemetry channels, varying greatly in their response from one device to another and susceptible to problems with drift, change with temperature, and battery condition. The inaccuracies in the peripheral (programmer) can compound the pacemaker and telemetry channel errors. In some cases, the accuracy of a telemetered intracardiac EGM signal from an implanted pacemaker may be only .+-.35%.